86 Essays in Biochemistry 



two stereoisomeric forms. Elimination of the 2-carbon side chain 

 occurs with certain pregnane derivatives, and oxidation of hydroxy! 

 groups to ketones sometimes takes place. The reductive processes 

 usually proceed with a high degree of stereochemical specificity, and 

 although both possible isomers may be formed they are usually found 

 in unequal amounts. The structure of the compounds exerts a decisive 

 influence on the relative amounts of epimers formed, and in vivo the 

 metabolic status of the subject may have a lesser effect. 



The examination of steroid-hormone metabolites in the urine of 

 normal and diseased persons has yielded a rich harvest of compounds 

 which delineate the general pattern of degradation of the secreted 

 hormones. Over and above the purely scientific interest which attaches 

 to tracing the metabolism of these biologically important substances, 

 there is intense interest on the part of clinicians in the role of the steroid 

 hormones in various disease processes and in the utilization of urinary 

 steroid analyses as diagnostic and prognostic tools. An enormous litera- 

 ture has grown up in this field, and there can be little doubt that these 

 procedures are firmly established in good clinical practice. 



However, there are certain points of interpretation of the data which 

 merit closer inquiry. Urinary steroid analyses find their greatest use 

 in the detection of hypo- and hyperfunction of the adrenal cortex and, 

 to a lesser extent, the gonads. These diseases may be tentatively con- 

 sidered as primary diseases of steroid-hormone biosynthesis; normally 

 occurring enzyme systems may be either increased or decreased in 

 amount, but it is improbable that new pathways are introduced. Thus 

 the clinical manifestations of the disease are the result of hyper- or 

 hypostimulation of the target tissues by normal secretory products of 

 the gonads or adrenal cortex. Alternatively, intermediates may be 

 present in excessive amounts owing to absence or deficiency of enzyme 

 systems required for the elaboration of the normal product. The effects 

 seen are also modified by the inherent responsiveness of the target 

 tissues. 



There are certain other diseases in which abnormalities of steroid 

 metabolism have been postulated on the basis of less direct evidence. 

 These include neoplastic disease and the collagen diseases. In the 

 former group the evidence, which is particularly strong in the case of 

 cancer of the breast and prostate gland, revolves about the palliative 

 effects of the removal of the gonads and adrenal cortex and/or the 

 administration of certain steroid hormones or corticotropin. In the 

 collagen diseases, the evidence is likewise based upon the effect of 

 cortical steroids and ACTH in modifying the symptoms of disease. 



